原发性肝癌合并门静脉癌栓的外科治疗

肝癌是常见恶性肿瘤之一，其发病率和病死率居我国恶性肿瘤第二位。门静脉侵犯是肝癌重要的生物学特性。肝癌倾向于侵袭门静脉，并继而形成癌栓。临床报道肝癌门静脉癌栓（PVTT）发生率为44．0％～62．2％。肝癌侵袭门静脉是肝内播散及根治性切除术后早期复发的根源。此外，癌栓阻塞门静脉，门静脉高压加剧，继而引发食道胃底静脉破裂出血，甚至导致肝功能衰竭。因此，肝癌合并PVTT患者总体预后差，中位生存时间仅2．7个月。     

Hepatic arterial infusion chemotherapy for hepatocellular carcinoma with portal vein tumor thrombosis

AIM: Hepatocellular carcinoma (HCC) with portal vein tumor thrombosis (PVTT) is associated with poor prognosis. The aim of this prospective study was to evaluate the efficacy of hepatic arterial infusion chemotherapy (HAIC) for patients with this disease. METHODS: Eighteen HCC patients with PVTT were treated with HAIC via a subcutaneously implanted injection port. A course of chemotherapy consisted of daily cisplatin (10 mg for one hour) followed by 5-fluorouracil (250 mg for five hours) for five continuous days within a given week. The patients were scheduled to receive four consecutive courses of HAIC. Responders were defined in whom either a complete or partial response was achieved, while non-responders were defined based on stable or progressive disease status. The prognostic factors associated with survival after treatment were analyzed. RESULTS: Six patients exhibited partial response to this form of HAIC (response rate=33%). The 3, 6, 9, 12 and 18-month cumulative survival rates for the 18 patients were 83%, 72%, 50%, 28%, and 7%, respectively. Median survival times for the six responders and 12 non-responders were 15.0 (range, 11-18) and 7.5 (range, 1-13) months, respectively. It was demonstrated by both univariate and multivariate analyses that the therapeutic response and hepatic reserve function were significant prognostic factors. CONCLUSION: HAIC using low-dose cisplatin and 5-fluorouracil may be a useful alternative for the treatment of patients with advanced HCC complicated with PVTT. There may also be survival-related benefits associated with HAIC.     

Radiotherapy as valid modality for hepatocellular carcinoma with portal vein tumor thrombosis

Although the current standard treatment for hepatocellular carcinoma(HCC) with portal vein tumor thrombosis(PVTT) is sorafenib, many previous studies have established the need for a reliable local modality for PVTT control, which is a major cause of liver function deterioration and metastasis. Additionally, there is growing evidence for the prognostic significance of PVTT classification according to the location of tumor thrombosis. Favorable outcomes can be obtained by applying local modalities, including surgery or transarterial chemoembolization, especially in second-order or distal branch PVTT. Rapid control of PVTT could maintain or improve liver function and reduce intrahepatic as well as distant metastasis. Radiotherapy(RT) is one of the main locoregional treatment modalities in oncologic fields, but has rarely been used in HCC because of concerns regarding hepatic toxicity. However, with the development of advanced techniques, RT has been increasingly applied in HCC management. Randomized studies have yet to definitively prove the benefit of RT, but several comparative studies have justified the application of RT in HCC. The value of RT is especially noticeable in HCC with PVTT; several prospective and retrospective studies have reported favorable outcomes, including a 40% to 60% objective response rate and median overall survival of 15 mo to 20 mo in responders. In this review, we evaluate the role of RT as an alternative local modality in HCC with PVTT.     

Post-hepatectomy survival in advanced hepatocellular carcinoma with portal vein tumor thrombosis

AIM: To analyze hepatocellular carcinoma(HCC) patients with portal vein tumor thrombosis(PVTT) using the tumor-node-metastasis(TNM) staging system.METHODS: We retrospectively analyzed 372 patients with HCC who underwent hepatectomy between 1980 and 2009.We studied the outcomes of HCC patients with PVTT to evaluate the American Joint Committee on Cancer TNM staging system(7th edition) for stratifying and predicting the prognosis of a large cohort of HCC patients after hepatectomy in a single-center.Portal vein invasion(vp) 1 was defined as an invasion or tumor thrombus distal to the second branch of the portal vein,vp2 as an invasion or tumor thrombus in the second branch of the portal vein,vp3 as an invasion or tumor thrombus in the first branch of the portal vein,and vp4 as an invasion or tumor thrombus in the portal trunk or extending to a branch on the contralateral side.RESULTS: The cumulative 5-year overall survival(5yr OS) and 5-year disease-free survival(5yr DFS) rates of the 372 patients were 58.3% and 31.3%,respectively.The 5yr DFS and 5yr OS of vp3-4 patients(n = 10) were 20.0%,and 30.0%,respectively,which was comparable with the corresponding survival rates of vp1-2 patients(P = 0.466 and 0.586,respectively).In the subgroup analysis of patients with macroscopic PVTT(vp2-4),the OS of the patients who underwent preoperative transarterial chemoembolization was comparable to that of patients who did not(P = 0.747).There was a significant difference in the DFS between patients with stage Ⅰ HCC and those with stage Ⅱ HCC(5yr DFS 39.2% vs 23.1%,P 0.001); however,theDFS for stage Ⅱ was similar to that for stage Ⅲ(5yrD FS 23.1% vs 13.8%,P = 0.330).In the subgroup analysis of stage Ⅱ-Ⅲ HCC(n = 148),only alpha-fetoprotein(AFP) 100 mg/dL was independently associated with DFS.CONCLUSION: Hepatectomy for vp3-4 HCC results in a survival rate similar to hepatectomy for vp1-2.AFP stratified the stage Ⅱ-Ⅲ HCC patients according to prognosis.     

肝细胞癌伴门静脉癌栓的介入综合治疗

伴门静脉癌栓(PVTT)的肝细胞癌(HCC)常见于进展期肝癌,PVTT可引起肿瘤播散、肝功能衰竭和门静脉高压,从而导致顽固性腹水、静脉曲张破裂和肝性脑病,严重影响肝癌患者预后。根据巴塞罗那临床肝癌分期(BCLC),伴PVTT的进展期HCC,索拉非尼被推荐为一线治疗方案,但由于其疗效有限且价格昂贵限制了它在国内的应用。而介入治疗以其微创、可重复性等优点在临床得到广泛应用,并取得一定的疗效。目前主要应用的介入治疗方法包括:经肝动脉灌注化疗术(HAIC)、经肝动脉化疗栓塞术(TACE)、TACE联合索拉非尼、TACE联合消融术、TACE联合适形放疗、TACE联合门静脉支架、门静脉粒子条置放术、经颈静脉肝内门体分流术(TIPS)等。最后指出多种方法综合治疗有望取得较好疗效。     

超声评估门静脉与HCC患者肝移植预后的关系

目的:探讨超声检查肝细胞癌(hepatocellular carcinoma,HCC)门静脉对肝移植患者预后的诊断价值.方法:收集2000-01/2006-10四川大学华西医院进行肝移植的HCC患者148例,结合患者超声、病理以及临床资料,对患者肝移植后生存情况进行回顾性分析.结果:全组随访时间2.8-69.5(平均16.4)mo.随访期间,肿瘤复发率为43.2%.超声检查无门静脉受累者102例(68.9%),门静脉肝内分支受累者32例(21.6%),门静脉主干受累者14例(9.5%).单因素COX模型分析结果显示:门静脉受累是对累积生存率和无瘤生存率有统计学意义的协变量(RR=2.673,P=0.000).多因素COX逐步回归分析结果显示:门静脉受累是对累积生存率(RR=2.426,P=0.000)和无瘤生存率(RR=2.258,P=0.000)有影响的独立因素.结论:门静脉受累是独立性的预后影响因素,超声检测HCC患者门静脉是否受累有助于患者适应证的选择.     

Efficacy of different treatment strategies for hepatocellular carcinoma with portal vein tumor thrombosis

AIM: To evaluate the efficacy of different treatment strategies for hepatocellular carcinoma (HCC) with portal vein tumor thrombosis (PVTT) and investigate factors influencing prognosis. METHODS: One hundred and seventy-nine HCC patients with macroscopic PVTT were enrolled in this study. They were divided into four groups and underwent different treatments: conservative treatment group (n = 18), chemotherapy group (n = 53), surgical resection group (n = 24) and surgical resection with postoperative chemotherapy group (n = 84). Survival rates of the patients were analyzed by the Kaplan-Meier method. A log-rank analysis was performed to identify group differences. Cox's proportional hazards model was used to analyze variables associated with survival. RESULTS: The mean survival periods of the patients in four groups were 3.6, 7.3,10.1, and 15.1 mo respectively. There were significant differences in the survival rates among the groups. The survival rates at 0.5-, 1-, 2-, and 3-year in surgical resection with postoperative chemotherapy group were 55.8%, 39.3%, 30.4%, and 15.6% respectively, which were significantly higher than those of other groups (p<0.001). Multivariate analysis revealed that the strategy of treatment (P<0.001) and the number of chemotherapy cycles (P = 0.012) were independent survival predictors for patients with HCC and PVTT. CONCLUSION: Surgical resection of HCC and PVTT combined with postoperative chemotherapy or chemoembolization is the most effective therapeutic strategy for the patients who can tolerate operation. Multiple chemotherapeutic courses should be given postoperatively to the patients with good hepatic function reserve.     

Quantitative comparison of ~(68)Ga-NGR and ~(18)F-FDG uptake in well-differentiated hepatocellular carcinoma bearing mice

正Objective To quantitatively compare the diagnostic capability of ~(68)Ga-NGR and ~(18)F-FDG in well-differentiated hepatocellular carcinoma(HCC)bearing mice by micro PET/CT imaging.Methods The in vitro cellular uptake,in vivo micro PET/CT imaging and biodistribution studies of ~(68)Ga-NGR and~(18)F-FDG were quantitatively compared in SMMC-7721-based well-differentiated HCC.The human fibrosarcoma(HT-1080)and human colorec-     

Hepatic arterial infusion chemotherapy in hepatocellular carcinoma with portal vein tumor thrombosis

AIM: To evaluate the prognostic factors and efficacy of hepatic arterial infusion chemotherapy in hepatocellular carcinoma with portal vein tumor thrombosis. METHODS: Fifty hepatocellular carcinoma (HCC) patients with portal vein tumor thrombosis (PVTT) were treated using hepatic arterial infusion chemotherapy (HAIC) via a subcutaneously implanted port. The epirubicin-cisplatin-5-fluorouracil (ECF) chemotherapeutic regimen consisted of 35 mg/m 2 epirubicin on day 1, 60 mg/m 2 cisplatin for 2 h on day 2, and 500 mg/m 2 5-fluorouracil for 5 h on days 1-3. The treatments were repeated every 3 or 4 wk. RESULTS: Three (6%) of the 50 patients achieved a complete response (CR), 13 (26%) showed partial responses (PR), and 22 (44%) had stable disease (SD).The median survival and time to progression were 7 and 2 mo, respectively. After 2 cycles of HAIC, CR was achieved in 1 patient (2%), PR in 10 patients (20%) and SD in 26 patients (52%). Significant pre-treatment prognostic factors were a tumor volume of < 400 cm 3 (P = 0.01) and normal levels of protein induced by vitamin K absence or antagonist (PIVKA)-Ⅱ (P = 0.022). After 2 cycles of treatment, disease control (CR + PR + SD) (P = 0.001), PVTT response (P = 0.003) and α-fetoprotein reduction of over 50% (P = 0.02) were independent factors for survival. Objective response (CR + PR), disease control, PVTT response, and combination therapy during the HAIC were also significant prognostic factors. Adverse events were tolerable and successfully managed. CONCLUSION: HAIC may be an effective treatment modality for advanced HCC with PVTT in patients with tumors < 400 cm 3 and good prognostic factors.     

Management of hepatocellular carcinoma patients with portal vein tumor thrombosis: A narrative review

Background: Hepatocellular carcinoma(HCC) is one of the main reasons for malignancy-related death. Portal vein tumor thrombosis(PVTT) is the most common form of macrovascular invasion related to HCC occurring in 10%-60% of patients. HCC with PVTT is usually characterized by worsening liver function, vulnerability to blood metastasis, higher incidence of complications associated with portal hypertension, and intolerance to treatment when compared with that without PVTT. If only treated with suppo...     

Sorafenib for recurrence of hepatocellular carcinoma after liver transplantation

BackgroundRecurrence of hepatocellular carcinoma after orthotopic liver transplantation not amenable to surgical approaches is associated with poor outcome.AimsRetrospective evaluation of the safety and efficacy of sorafenib in patients with post-transplant hepatocellular carcinoma recurrence.MethodsPatients with post-transplant hepatocellular carcinoma recurrence were treated with sorafenib. Adverse events were assessed using National Cancer Institute Common Toxicity Criteria of AEs version 3.0, tumour response was evaluated according to Response Evaluation Criteria in Solid Tumours.ResultsFirst-line therapy after recurrence was surgery (n = 6), radiation therapy (n = 1), chemotherapy (n = 1), and sorafenib (n = 3). Finally, 11 patients were treated with sorafenib. Nine patients (82%) received an additionally targeted therapy with sirolimus as part of their immunosuppressive regimen. Most common grade 3 adverse events included diarrhoea (46%), hand-foot skin reaction (27%), nausea, fatigue, and leucopoenia (all 18%). Sorafenib had to be discontinued in two patients due to adverse events and six additional patients required a dose adjustment. No deterioration of liver graft function occurred. Median time to progression was 4.1 months; however, patients were treated with ongoing sorafenib in case of clinical benefit (median 8.9 months). Median overall survival after initiation of sorafenib treatment was 20.1 months.ConclusionSorafenib in combination with immunosuppression including sirolimus may be administered to patients with post-transplant hepatocellular carcinoma recurrence with acceptable toxicity and without deterioration of liver graft function.     

Microwave ablation of hepatocellular carcinoma with portal vein tumor thrombosis after transarterial chemoembolization: a prospective study

Aims

To prospectively assess the use of microwave ablation (MWA) to treat hepatocellular carcinoma (HCC) with portal vein tumor thrombosis (PVTT) after transarterial chemoembolization (TACE), and to evaluate factors that significantly affect treatment outcomes.

Methods

Sixty patients with HCC [55 male, 5 female; mean age, 54.1 ± 10.2 (range 36–77) years] + PVTT were enrolled. Patients were treated with MWA after TACE. Results were compared with those of 54 patients treated by TACE alone in another retrospective study. Data analyzed included patient demographics, Eastern Cooperative Oncology Group performance status, liver cirrhosis, liver volume, Child-Pugh class, Cancer of the Liver Italian Program (CLIP) score, and imaging findings. Survival time (from occurrence of PVTT to last follow-up) and predictive factors and their correlation with survival were statistically evaluated.

Results

The median 3-year overall survival (OS) duration was 13.5 months, and the 1- and 3-year OS rates were 48 and 23 %, respectively. Cox hazards regression analysis revealed that change in the neutrophil-to-lymphocyte ratio, CLIP score, and treatment efficacy were the only independent predictive factors for outcome (p = 0.035, 0.024, and 0.000, respectively).

Conclusions

Combination therapy with MWA after TACE may provide a substantial benefit for patients with HCC + PVTT type I, II, or partial III and Child-Pugh class A or B by reducing the tumor burden.

Trial registration number

Chinese Clinical Trial Register (ChiCTR): ChiCTR-ONC-12002689.

     

Transcatheter arterial embolization for hepatocellular carcinoma with portal vein thrombosis

Abstract In order to evaluate the possible benefits of transcatheter arterial embolization (TAE) in hepatocellular carcinoma (HCC) patients with peripheral portal vein thrombosis, 96 consecutive HCC cases with peripheral portal vein thrombosis were analysed. Of them, 35 cases received TAE and 61 cases did not. Most (77.8%) of the TAE-treated cases showed decreased α-fetoprotein (AFP) levels after treatment, but 57.1% of them suffered another rise in AFP levels and subsequently died. One patient (2.8%) developed progressive jaundice after TAE and died within 1 month, while four of the non-TAE cases died within 1 month after diagnosis. In general, TAE is safe for HCC patients with peripheral portal vein thrombosis. In addition, using Cox's regression model for multivariate survival analysis, serum total bilirubin (≤, > 2 mg/dL; P = 0.0254), AFP (≤ 3155 ng/mL, > 3155 ng/mL; P = 0.0002) and treatments (TAE, non-TAE; P = 0.0059) were found to affect their prognosis. There was significant difference in survival between TAE and non-TAE groups, the 6 month, 1 year and 2 year survival rates were 91.4 versus 62.3%, 51.4 versus 26.2% and 17.1 versus 4.9% ( P = 0.0017). The median survival times of TAE and non-TAE groups were 10.3 versus 3.7 months, respectively. Though TAE only provided palliative treatment, it did prolong survival in HCC patients with peripheral portal vein thrombosis.     

Spontaneous regression of diffuse intrahepatic recurrence with portal vein tumor thrombus after resection of hepatocellular carcinoma

We report a rare case of spontaneous regression of diffuse intrahepatic recurrence with portal vein tumor thrombus (PVTT) after resection of hepatocellular carcinoma (HCC). A 68-year-old man with hepatitis C virus-related liver cirrhosis presented with a 40 mm tumor in the right anterior segment of the liver. The tumor was diagnosed as HCC by typical imaging findings and elevated serum alpha-fetoprotein (AFP) (716 ng/ml) and protein induced by vitamin K absence II (PIVKA II) (8,100 ng/ml). A right anterior sectionectomy of the liver was performed. Microscopically, the tumor was moderately differentiated HCC. Four months after resection, a computed tomography (CT) scan showed diffuse intrahepatic recurrence with PVTT. Serum AFP was 12,319 ng/ml and PIVKA II was 168,000 ng/ml. The patient did not receive any further treatment for HCC including herbal medicine, and stopped smoking. Two years and 5 months later, no lesion was detected on a CT scan when serum AFP was 1.9 ng/ml. Ischemia due to main portal vein occlusion and rapid tumor growth might have induced tumor regression in the present case. Moreover, abstention from smoking might have improved his immunological function.     

Transjugular intrahepatic portosystemic shunt with covered stents for hepatocellular carcinoma with portal vein tumor thrombosis

AIM: To evaluate transjugular intrahepatic portosystemic shunt(TIPS) with covered stents for hepatocellular carcinoma(HCC) with main portal vein tumor thrombus(PVTT). METHODS: Eleven advanced HCC patients(all male, aged 37-78 years, mean: 54.3 ± 12.7 years) presented with acute massive upper gastrointestinal bleeding(n = 9) or refractory ascites(n = 2) due to tumor thrombus in the main portal vein. The diagnosis of PVTT was based on contrast-enhanced computed tomography and color Doppler sonography. The patients underwent TIPS with covered stents. Clinical characteristics and average survival time of 11 patients were analyzed. Portal vein pressure was assessed before and after TIPS. The follow-up period was 2-18 mo. RESULTS: TIPS with covered stents was successfully completed in all 11 patients. The mean portal vein pressure was reduced from 32.0 to 11.8 mmHg(t = 10.756, P = 0.000). Gastrointestinal bleeding was stopped in nine patients. Refractory ascites completely disappeared in one patient and was alleviated in another. Hepatic encephalopathy was observed in six patients and was resolved with drug therapy. During the follow-up, ultrasound indicated the patency of the shunt and there was no recurrence of symptoms. Death occurred 2-14 mo(mean: 5.67 mo) after TIPS in nine cases, which were all due to multiple organ failure. In the remaining two cases, the patients were still alive at the 16- and 18-mo follow-up, respectively. CONCLUSION: TIPS with covered stents for HCC patients with tumor thrombus in the main portal vein is technically feasible, and short-term efficacy is favorable.